This invention relates to acetals of rapamycin, their immunosuppressant properties and their antifungal activity. This invention further relates to pharmaceutical compositions containing rapamycin acetals.
Rapamycin is a macrolide antibiotic produced by Streptomyces hydroscopicus having profound antifungal activity, especially against Candida albicans, and low toxicity [U.S. Pat. Nos. 3,929,992 and 3,993,749; Journal of Antibiotics 28(10), 721-726, 727-732 (1975) and journal of Antibiotics 31(6), 539-545 (1978)].
Rapamycin was reported to inhibit the immune response in Can. J. Physiol. Pharmacol. 55, 48-51 (1977). U.S. Pat. No. 4,316,885 discloses monoacyl and diacyl derivatives of rapamycin, especially the acetylated derivatives which are useful antifungal antibiotics. A. U.S. Pat. application Ser. No. 957,626 filed Nov. 3, 1978 which ultimately resulted in U.S. Pat. No. 4,885,171 discloses a method for treating carcinogenic tumors in mammals with rapamycin. U.S. Pat. No. 4,401,653 discloses a method of using rapamycin and picibanil in combination for the treatment of transplantable carcinogenic tumors. U.S. Pat. No. 4,650,803 discloses aminoalkylcarboxylic acid esters of rapamycin at positions 31 and/or 42 which are water soluble prodrug forms of rapamycin.